Anti-ROR1 antibodies and methods of making and using thereof

ABSTRACT

The application provides anti-ROR1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of filing dates of U.S. Provisional Patent Application No. 62/551,035, filed Aug. 28, 2017, U.S. Provisional Patent Application No. 62/551,032 filed Aug. 28, 2017, U.S. Provisional Patent Application No. 62/524,554 filed Jun. 25, 2017, U.S. Provisional Patent Application No. 62/524,557 filed Jun. 25, 2017, U.S. Provisional Patent Application No. 62/524,558 filed Jun. 25, 2017, U.S. Provisional Patent Application No. 62/545,603 filed Aug. 15, 2017, U.S. Provisional Patent Application No. 62/551,032 filed Aug. 28, 2017, and U.S. Provisional Patent Application No. 62/551,065 filed Aug. 28, 2017, the entire disclosures of which are expressly incorporated by reference herein.

TECHNICAL FIELD

The present disclosure generally relates to the technical field of antibodies, and more particularly relates to making and using anti-ROR1 antibodies.

BACKGROUND

Cancer is a major health problem across the world. In the United States alone it is estimated that in 2016 there were 1,685,210 new cases of cancer diagnosed and 595,690 deaths from the disease (http://www.cancer.gov). As such, any pharmaceutical agent that can reduce the severity or mortality rate from cancer is desirable.

In the immune system, resting T-cells can be activated to respond to antigen through a primary signal delivered through the T-cell receptor (TCR) by foreign antigen peptides presented by antigen-presenting cells (APCs). In addition to this primary signal, there are secondary positive and negative co-stimulatory signals that further influence the response of the T-cells. A secondary positive signal is required for full T-cell activation (see, Lafferty et al., Ausl. J. Exp. Biol. Med. Sci. 53: 27-42, 1975). Negative secondary signals can result in T-cell suppression and tolerance.

Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is an enzyme that in humans is encoded by the ROR1 gene. (see, Masiakowski P and Carroll R D, J. Bio. Chem. 267 (36): 26181-90. 1992; Reddy U R, et al, Oncogene. 13 (7): 1555-9, 1996). ROR1 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family. ROR1 has recently been shown to be expressed on ovarian cancer stem cell, on which it seems to play a functional role in promoting migration/invasion or spheroid formation in vitro and tumour engraftment in immune-deficient mice. Treatment with a humanized mAb specific for ROR1 (UC-961) could inhibit the capacity of ovarian cancer cells to migrate, form spheroids, or engraft immune-deficient mice. Moreover, such treatment inhibited the growth of tumour xenografts, which in turn had a reduced capacity to engraft immune-deficient mice and were relatively depleted of cells with features of CSC, suggesting that treatment with UC-961 could impair CSC renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which may be targeted for anti-CSC therapy. (see, Zhang S, et al, PNAS. 111 (48): 17266-71, 2014).

ROR1 is expressed in a number of malignancies with low levels of expression in normal adult tissue. Much like the physiological functions of ROR1, ROR1 in cancer can have kinase activity-dependent or -independent function, which could be a result of tissue specific expression of co-receptor or effector proteins. The induction of apoptosis with ROR1 knockdown, EGFR signalling potentiation and ROR1-mediated upregulation of EMT genes support the notion that ROR1 plays an important role in cancer progression. Further research is required to elucidate the tumour-specific mechanisms of ROR1 overexpression and the contribution of ROR1 to initiation and progression of cancer.

SUMMARY

In one aspect, the present disclosure provides, among others, anti-ROR1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same.

In one embodiment, the disclosure provides one or more isolated monoclonal antibodies (mAb) or antigen-binding fragment thereof that binds specifically to human ROR1. In one embodiment, the isolated one or more mAb or antigen-binding fragment includes an antigenic peptide sequence having a sequence as disclosed herein. In one embodiment, the isolated mAb or antigen-binding fragment is selected from the sequences as disclosed herein.

In one embodiment, an isolated monoclonal antibody (mAb) or antigen-binding fragment have an amino acid sequence having a percentage homology with SEQ ID NO:4, SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, SEQ ID NO:20, SEQ ID NO:24, SEQ ID NO:28, SEQ ID NO:32, SEQ ID NO:36, SEQ ID NO:40, SEQ ID NO:44, SEQ ID NO:48, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:60, SEQ ID NO:64, SEQ ID NO:68, SEQ ID NO:72, SEQ ID NO:76, SEQ ID NO:80, SEQ ID NO:84, SEQ ID NO:88, SEQ ID NO:88, SEQ ID NO:92, SEQ ID NO:96, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:108, SEQ ID NO:112, SEQ ID NO:116, SEQ ID NO:120, SEQ ID NO:124, SEQ ID NO:128, or SEQ ID NO:132. In one embodiment, the percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%

In one embodiment, the isolated one or more mAb or antigen-binding fragment has a binding affinity to ROR1 with a Kd not greater than 30 nM, 40 nM, 50 nM, 60 nM, 70 nM, 80 nM, 90 nM or 100 nM. In one embodiment, the ROR1 is a human ROR1.

In one embodiment, the isolated mAb or antigen-binding fragment exhibits one or more functional properties. Example functional properties include without limitation high affinity binding to ROR1, enhancing T cell activation, the ability to stimulate antibody responses and/or the ability to reverse the suppressive function of immunosuppressive cells, such as T regulatory cells. In one embodiment, the enhancing T-cell activation comprises T-cell proliferation, IFN-γ and/or IL-2 secretion, or a combination thereof. In one embodiment, the immunosuppressive cell comprises a regulatory cell.

In one embodiment, the isolated mAb or antigen-binding fragment comprises a human framework region. In one embodiment, the isolated mAb or antigen-binding fragment is a humanized antibody, a chimeric antibody, or a recombinant antibody.

In one embodiment, the isolated mAb or antigen-binding fragment is an IgG. In one embodiment, the antigen-binding fragment is a Fv, a Fab, a F(ab′)2, a scFV or a scFV2 fragment. In one embodiment, the isolated mAb is a bispecific antibody, tri-specific antibody, or multi-specific antibody.

In one embodiment, the application provides an isolated mAb or antigen-binding fragment having a binding specificity to ROR1 and an IgG1 heavy chain. The IgG heavy chain comprises an amino acid sequence having a percentage homology with SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:23, SEQ ID NO:31, SEQ ID NO:39, SEQ ID NO:47, SEQ ID NO:55, SEQ ID NO:63, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:87, SEQ ID NO:91, SEQ ID NO:99, SEQ ID NO:107, SEQ ID NO:115, SEQ ID NO:123, or SEQ ID NO:131. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%.

In one embodiment, the application provides an isolated mAb or antigen-binding fragment having a binding specificity to ROR1 and a kappa light chain. The kappa light chain comprises an amino acid sequence having a percentage homology with SEQ ID NO:3, SEQ ID NO:11, SEQ ID NO:19, SEQ ID NO:27, SEQ ID NO:35, SEQ ID NO:43, SEQ ID NO:51, SEQ ID NO:59, SEQ ID NO:67, SEQ ID NO:75, SEQ ID NO:83, SEQ ID NO:95, SEQ ID NO:103, SEQ ID NO:111, SEQ ID NO:119, or SEQ ID NO:127. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%.

In one embodiment, the application provides an isolated mAb or antigen-binding fragment having a binding specificity to ROR1 and a variable light chain. The variable chain comprises an amino acid sequence having a percentage homology with SEQ ID NO:4, SEQ ID NO:12, SEQ ID NO:20, SEQ ID NO:28, SEQ ID NO:36, SEQ ID NO:44, SEQ ID NO:52, SEQ ID NO:60, SEQ ID NO: 68, SEQ ID NO:76, SEQ ID NO:84, SEQ ID NO:96, SEQ ID NO:104, SEQ ID NO:112, SEQ ID NO:120, or SEQ ID NO:128. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%.

In one embodiment, the application provides an isolated mAb or antigen-binding fragment having a binding specificity to ROR1 and a variable heavy chain. The variable heavy chain comprises an amino acid sequence having at least 90% identity with SEQ ID NO:8, SEQ ID NO:16, SEQ ID NO:24, SEQ ID NO:32, SEQ ID NO:40, SEQ ID NO:48, SEQ ID NO:56, SEQ ID NO:64, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:88, SEQ ID NO:92, SEQ ID NO:100, SEQ ID NO:108, SEQ ID NO:116, SEQ ID NO:124, or SEQ ID NO:132. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%.

The application further provides isolated nucleic acids encode at least a portion of the isolated mAb or antigen-binding fragment disclosed herein. In one embodiment, the isolated mAb or antigen-binding fragment has a percentage homology with the IgG1 heavy chain SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:23, SEQ ID NO:31, SEQ ID NO:39, SEQ ID NO:47, SEQ ID NO:55, SEQ ID NO:63, SEQ ID NO:71, SEQ ID NO:79, SEQ ID NO:87, SEQ ID NO:91, SEQ ID NO:99, SEQ ID NO:107, SEQ ID NO:115, SEQ ID NO:123, or SEQ ID NO:131. In one embodiment, the isolated mAb or antigen-binding fragment has a percentage homology with the kappa light: SEQ ID NO:3, SEQ ID NO:11, SEQ ID NO:19, SEQ ID NO:27, SEQ ID NO:35, SEQ ID NO:43, SEQ ID NO:51, SEQ ID NO:59, SEQ ID NO:67, SEQ ID NO:75, SEQ ID NO:83, SEQ ID NO:95, SEQ ID NO:103, SEQ ID NO:111, SEQ ID NO:119, or SEQ ID NO:127. In one embodiment, the isolated mAb or antigen-binding fragment has a percentage homology with the the variable light chain: SEQ ID NO:4, SEQ ID NO:12, SEQ ID NO:20, SEQ ID NO:28, SEQ ID NO:36, SEQ ID NO:44, SEQ ID NO:52, SEQ ID NO:60, SEQ ID NO: 68, SEQ ID NO:76, SEQ ID NO:84, SEQ ID NO:96, SEQ ID NO:104, SEQ ID NO:112, SEQ ID NO:120, or SEQ ID NO:128. In one embodiment, the isolated mAb or antigen-binding fragment has a percentage homology with the variable heavy: SEQ ID NO:8, SEQ ID NO:16, SEQ ID NO:24, SEQ ID NO:32, SEQ ID NO:40, SEQ ID NO:48, SEQ ID NO:56, SEQ ID NO:64, SEQ ID NO:72, SEQ ID NO:80, SEQ ID NO:88, SEQ ID NO:92, SEQ ID NO:100, SEQ ID NO:108, SEQ ID NO:116, SEQ ID NO:124, or SEQ ID NO:132. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%.

The application further provides expression vectors containing the isolated nucleic acid encoding an amino acid sequence having a percentage homology with the amino acid sequences disclosed herein. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%. In one embodiment, the expression vector is expressible in a cell.

The application further provides host cells comprising nucleic acids that encode an amino acid sequence having a percentage homology with the amino acid sequences disclosed herein. The percentage homology is not less than 70%, 80%, 90%, 95%, 98%, or 99%. In one embodiment, the host cell can be a prokaryotic cell or a eukaryotic cell.

In another aspect, the application provides methods for producing an antibody or its antigen-binding fragment thereof having a binding specificity to human ROR1. In one embodiment, the method includes the steps of providing a host cell that contains an expression vector expressible in the host cell, the expression vector comprises nucleic acids encoding at least at portion of the isolated mAb or antigen-binding fragment, or peptides with at least 70%, 80%, 90%, 95%, 98%, or 99% identity, to produce an antibody by the expression of the nucleic acids.

The application further provides immuno-conjugates. In one embodiment, the immuno-conjugates include a drug unit or an imaging agent linked to an isolated mAb or antigen-binding fragment disclosed herein through a linker.

The linker may be cleavable or non-cleavable. In one embodiment, the linker is a chemical linker. In one embodiment, the linker comprises a covalent bond such as an ester bond, an ether bond, an amine bond, an amide bond, a disulphide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphorus ester bond, a peptide bond, a hydrazone bond or a combination thereof. In one embodiment, the linker comprises a hydrophobic poly(ethylene glycol) linker. In one embodiment, the linker comprises a peptide bond.

In one embodiment, the drug unit in the immuno-conjugate comprises a chemotherapeutic agent, a growth inhibitory agent, a cytotoxic agent from class of calicheamicin, an antimitotic agent, a toxin, a radioactive isotope, or a combination thereof. In one embodiment, the drug unit comprises a calicheamicin, ozogamicin, monomethyl auristatin E, emtansine, a derivative or a combination thereof. In one embodiment, the drug unit comprises a calicheamicin, ozogamicin, monomethyl auristatin E, emtansine, a derivative or a combination thereof.

In one embodiment, the drug unit is selected from a cytotoxic agent, an immune regulatory reagent, an imaging agent or a combination thereof. In one embodiment, the cytotoxic agent is selected from a growth inhibitory agent or a chemotherapeutic agent from a class of tubulin binders, DNA intercalators, DNA alkylators, enzyme inhibitors, immune modulators, antimetabolite agents, radioactive isotopes, or a combination thereof. In one embodiment, the cytotoxic agent is selected from a calicheamicin, ozogamicin, monomethyl auristatin E, emtansine, a derivative or a combination thereof. In one embodiment, the immune regulatory reagents activate or suppress immune cells, T cell, NK cell, B cell, macrophage, or dendritic cell.

In one embodiment, the imaging agent may be radionuclide, a florescent agent, a quantum dots, or a combination thereof.

The application further provides a pharmaceutical composition. In one embodiment, the pharmaceutical composition comprises the isolated mAb or antigen-binding fragment disclosed herein and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises an immuno-conjugate disclosed herein and pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition further a chemotherapeutic agent, a growth inhibitory agent, a drug unit from class of calicheamicin, an antimitotic agent, a toxin, a radioactive isotope, a toxin, a therapeutic agent, or a combination thereof.

In a further aspect, the application provides a method of treating a subject with a cancer using the isolated mAb or antigen-binding fragment thereof as disclosed herein. In one embodiment, the method comprises the step of administering to the subject an effective amount of the isolated mAb or antigen-binding fragment as disclosed herein.

In one embodiment, the method includes directly injecting into the tumour site an effective amount of the monoclonal antibodies, the antigen-binding fragment thereof, and the immuno-conjugates and disclosed herein.

Varieties of cancer may be treated using the disclosed mAB, antigen-binding fragment thereof, or compositions. In one embodiment, the cancer has cells that express ROR-1. Example cancers include without limitation breast cancer, colorectal cancer, pancreatic cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, non-small lung cell cancer, glioma, esophageal cancer, nasopharyngeal cancer, anal cancer, rectal cancer, gastric cancer, bladder cancer, cervical cancer, or brain cancer.

In one embodiment, the method further includes co-administering an effective amount of a therapeutic agent. Example therapeutic a chemotherapeutic agent, a growth inhibitory agent, a drug unit from class of calicheamicin, an antimitotic agent, a toxin, a radioactive isotope, an antibody, an enzyme, or a combination thereof. In one embodiment, the therapeutic agent can be capecitabine, cisplatin, Cyclophosphamide, methotrexate, 5-fluorouracil, Doxorubicin, cyclophosphamide, Mustine, vincristine, procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, Epirubicin, pemetrexed, folinic acid, gemicitabine, oxaliplatin, irinotecan, topotecan, camptothecin, docetaxel, paclitaxel, fulvestrant, tamoxifen, letrozole, exemestane, anastrozole, aminoglutethimide, testolactone, vorozole, formestane, fadrozole, letrozole, erlotinib, lafatinib, dasatinib, gefitinib, osimertinib, vandertanib, afatinib, imatinib, pazopinib, lapatinib, sunitinib, nilotinib, sorafenib, nab-palitaxel, Everolimus, temsirolimus, Dabrafenib, vemurafenib, trametinib, vintafolide, apatinib, crizotinib, periforsine, olaparib, Bortezomib, tofacitinib, or a derivative or a combination thereof.

The subject receiving treatment may be a human. In one embodiment, the application provides a solution comprising an effective concentration of the isolated mAb or an antigen-binding fragment disclosed herein, wherein the solution is blood plasma in a subject.

Still other embodiments will become readily apparent to those skilled in the art from the following detailed description, wherein are described embodiments by way of illustrating the best mode contemplated. As will be realized, other and different embodiments are possible and the embodiments' several details are capable of modifications in various obvious respects, all without departing from their spirit and the scope. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of this disclosure will become more fully apparent from the following description and appended claims, taken in conjunction with the accompanying drawings. Understanding that these drawings depict only several embodiments arranged in accordance with the disclosure and are, therefore, not to be considered limiting of its scope, the disclosure will be described with additional specificity and detail through use of the accompanying drawings, in which:

FIG. 1 provides immunization strategy of NZW rabbits with human or mouse ROR1;

FIG. 2 provides immunization timeline;

FIG. 3 shows the harvest of spleen and lymph tissue from ROR1-immunized rabbits;

FIG. 4 shows the summary of B cell culture screening for ROR1-specific IgG and screening of chimeric rabbit/human IgG;

FIG. 5 shows the binding and off-rate analysis of different ROR1-specific humanized rabbit antibodies; and

FIG. 6 is a graph showing analytic results of rabbit serum for human and mouse ROR1-specific IgG before and after immunization, according to one embodiment.

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, similar symbols typically identify similar components, unless context dictates otherwise. The illustrative embodiments described in the detailed description, drawings, and claims are not meant to be limiting. Other embodiments may be utilized, and other changes may be made, without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that the aspects of the present disclosure, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, separated, and designed in a wide variety of different configurations, all of which are explicitly contemplated herein.

The disclosure provides, among others, isolated antibodies having specificity against ROR1, antigen binding fragment thereof, methods of making such antibodies, bispecific or multi-specific molecules, antibody-drug conjugates and/or immuno-conjugates composed from such antibodies or antigen binding fragment, pharmaceutical compositions containing the antibodies or antigen binding fragment, bispecific or multi-specific molecules, antibody-drug conjugates and/or immuno-conjugates, and methods for using the disclosed antibodies, antigen binding fragments and compositions for treating cancer.

In one aspect, the application provides monoclonal antibodies that bind specifically to human or mouse ROR1. In one embodiment, antibodies exhibit one or more desirable functional properties, such as high affinity binding to ROR1. In one embodiment, the antibodies are derived from specific heavy and light chain amino acid sequences and/or structural features such as rabbit/human chimeric antibodies composed of specific amino acid sequences.

Monoclonal antibodies can be produced using various methods including mouse hybridoma or phage display (see Siegel. Transfus. Clin. Biol. 9:15-22 (2002) for a review) or from molecular cloning of antibodies directly from primary B cells (see Tiller. New Biotechnol. 28:453-7 (2011)). In one embodiment, antibodies were created by the immunization of rabbits with either human or mouse ROR1 extracellular domain (ECD) or HEK 293 cells transiently transfected with mouse or human ROR1. Rabbits are known to create antibodies of high affinity, diversity and specificity (Weber et al. Exp. Mol. Med. 49:e305). B cells from immunized animals were cultured in vitro and screened for the production of anti-ROR1 antibodies. The antibody variable genes were isolated using recombinant DNA techniques and the resulting antibodies were expressed recombinantly. This general method of antibody discovery is similar to that described in Seeber et al. PLOS One. 9:e86184 (2014).

The term “antibody” is used in the broadest sense and specifically covers single monoclonal antibodies (including agonist and antagonist antibodies), antibody compositions with polyepitopic specificity, as well as antibody fragments (e.g., Fab, F(ab′)₂, and Fv), so long as they exhibit the desired biological activity. In some embodiments, the antibody may be monoclonal, polyclonal, chimeric, single chain, bispecific or bi-effective, simianized, human and humanized antibodies as well as active fragments thereof. Examples of active fragments of molecules that bind to known antigens include Fab, F(ab′)₂, scFv and Fv fragments, including the products of an Fab immunoglobulin expression library and epitope-binding fragments of any of the antibodies and fragments mentioned above. In some embodiments, antibody may include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e. molecules that contain a binding site that immunospecifically bind an antigen. The immunoglobulin can be of any type (IgG, IgM, IgD, IgE, IgA and IgY) or class (IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclasses of immunoglobulin molecule. In one embodiment, the antibody may be whole antibodies and any antigen-binding fragment derived from the whole antibodies. A typical antibody refers to heterotetrameric protein comprising typically of two heavy (H) chains and two light (L) chains. Each heavy chain is comprised of a heavy chain variable domain (abbreviated as VH) and a heavy chain constant domain. Each light chain is comprised of a light chain variable domain (abbreviated as VL) and a light chain constant domain. The VH and VL regions can be further subdivided into domains of hypervariable complementarity determining regions (CDR), and more conserved regions called framework regions (FR). Each variable domain (either VH or VL) is typically composed of three CDRs and four FRs, arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from amino-terminus to carboxy-terminus. Within the variable regions of the light and heavy chains there are binding regions that interacts with the antigen.

The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, uncontaminated by other immunoglobulins. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by the hybridoma method first described by Kohler & Milstein, Nature, 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Pat. No. 4,816,567).

The monoclonal antibodies may include “chimeric” antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 [1984]).

Monoclonal antibodies can be produced using various methods including mouse hybridoma or phage display (see Siegel. Transfus. Clin. Biol. 9:15-22 (2002) for a review) or from molecular cloning of antibodies directly from primary B cells (see Tiller. New Biotechnol. 28:453-7 (2011)). In the present disclosure antibodies were created by the immunization of rabbits with both human PD-L1 protein and cells transiently expressing human PD-L1 on the cell surface. Rabbits are known to create antibodies of high affinity, diversity and specificity (Weber et al. Exp. Mol. Med. 49:e305). B cells from immunized animals were cultured in vitro and screened for the production of anti-PD-L1 antibodies. The antibody variable genes were isolated using recombinant DNA techniques and the resulting antibodies were expressed recombinantly and further screened for desired features such as ability to inhibit the binding of PD-L1 to PD-1, the ability to bind to non-human primate PD-L1 and the ability to enhance human T-cell activation. This general method of antibody discovery is similar to that described in Seeber et al. PLOS One. 9:e86184 (2014).

The term “antigen- or epitope-binding portion or fragment” refers to fragments of an antibody that are capable of binding to an antigen (ROR1 in this case). These fragments may be capable of the antigen-binding function and additional functions of the intact antibody. Examples of binding fragments include, but are not limited to a single-chain Fv fragment (scFv) consisting of the VL and VH domains of a single arm of an antibody connected in a single polypeptide chain by a synthetic linker or a Fab fragment which is a monovalent fragment consisting of the VL, constant light (CL), VH and constant heavy 1 (CH1) domains. Antibody fragments can be even smaller subfragments and can consist of domains as small as a single CDR domain, in particular the CDR3 regions from either the VL and/or VH domains (for example see Beiboer et al., J. Mol. Biol. 296:833-49 (2000)). Antibody fragments are produced using conventional methods known to those skilled in the art. The antibody fragments are can be screened for utility using the same techniques employed with intact antibodies.

The “antigen-or epitope-binding fragments” can be derived from an antibody of the present disclosure by a number of art-known techniques. For example, purified monoclonal antibodies can be cleaved with an enzyme, such as pepsin, and subjected to HPLC gel filtration. The appropriate fraction containing Fab fragments can then be collected and concentrated by membrane filtration and the like. For further description of general techniques for the isolation of active fragments of antibodies, see for example, Khaw, B. A. et al. J. Nucl. Med. 23:1011-1019 (1982); Rousseaux et al. Methods Enzymology, 121:663-69, Academic Press, 1986.

Papain digestion of antibodies produces two identical antigen binding fragments, called “Fab” fragments, each with a single antigen binding site, and a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab′)₂ fragment that has two antigen combining sites and is still capable of cross-linking antigen.

The Fab fragment may contain the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab′)₂ antibody fragments originally were produced as pairs of Fab′ fragments which have hinge cysteines between them. Other, chemical couplings of antibody fragments are also known.

“Fv” is the minimum antibody fragment which contains a complete antigen recognition and binding site. This region consists of a dimer of one heavy and one light chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

The “light chains” of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda (A), based on the amino acid sequences of their constant domains.

Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgG-1, IgG-2, IgG-3, and IgG-4; IgA-1 and IgA-2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, delta, epsilon, γ, and μ, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known.

A “humanized antibody” refers to a type of engineered antibody having its CDRs derived from a non-human donor immunoglobulin, the remaining immunoglobulin-derived parts of the molecule being derived from one (or more) human immunoglobulin(s). In addition, framework support residues may be altered to preserve binding affinity. Methods to obtain “humanized antibodies” are well known to those skilled in the art. (see, e.g., Queen et al., Proc. Natl Acad Sci USA, 86:10029-10032 (1989), Hodgson et al., Bio/Technology, 9:421 (1991)).

The terms “polypeptide”, “peptide”, and “protein”, as used herein, are interchangeable and are defined to mean a biomolecule composed of amino acids linked by a peptide bond.

The terms “a”, “an” and “the” as used herein are defined to mean “one or more” and include the plural unless the context is inappropriate.

By “isolated” is meant a biological molecule free from at least some of the components with which it naturally occurs. “Isolated,” when used to describe the various polypeptides disclosed herein, means a polypeptide that has been identified and separated and/or recovered from a cell or cell culture from which it was expressed. Ordinarily, an isolated polypeptide will be prepared by at least one purification step. An “isolated antibody,” refers to an antibody which is substantially free of other antibodies having different antigenic specificities.

“Recombinant” means the antibodies are generated using recombinant nucleic acid techniques in exogeneous host cells.

The term “antigen” refers to an entity or fragment thereof which can induce an immune response in an organism, particularly an animal, more particularly a mammal including a human. The term includes immunogens and regions thereof responsible for antigenicity or antigenic determinants.

“Specific binding” or “specifically binds to” or is “specific for” a particular antigen or an epitope means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

Specific binding for a particular antigen or an epitope can be exhibited, for example, by an antibody having a KD for an antigen or epitope of at least about 10⁻⁴ M, at least about 10⁻⁵ M, at least about 10⁻⁶ M, at least about 10⁻⁷ M, at least about 10⁻⁸ M, at least about 10⁻⁹ M, alternatively at least about 10⁻¹⁰ M, at least about 10⁻¹¹ M, at least about 10⁻¹² M, or greater, where KD refers to a dissociation rate of a particular antibody-antigen interaction. Typically, an antibody that specifically binds an antigen will have a KD that is 20-, 50-, 100-, 500-, 1000-, 5,000-, 10,000- or more times greater for a control molecule relative to the antigen or epitope.

“Homology” between two sequences is determined by sequence identity. If two sequences which are to be compared with each other differ in length, sequence identity preferably relates to the percentage of the nucleotide residues of the shorter sequence which are identical with the nucleotide residues of the longer sequence. Sequence identity can be determined conventionally with the use of computer programs. The deviations appearing in the comparison between a given sequence and the above-described sequences of the disclosure may be caused for instance by addition, deletion, substitution, insertion or recombination.

The application further provides immuno-conjugates including a drug unit linked to the antibodies and antigen-binding fragments disclosed herein through a linker. The linker may be cleavable or noncleavable. In one embodiment, the linker is a chemical linker. In one embodiment, the linker comprises a covalent bond such as an ester bond, an ether bond, an amid bond, a disulphide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphorus ester bond, a peptide bond, or a combination thereof. In one embodiment, the linker comprises a hydrophobic poly(ethylene glycol) linker. In one embodiment, the linker comprises a peptide bond.

In one embodiment, the drug unit may be a chemotherapeutic agent, a growth inhibitory agent, a drug unit from class of calicheamicin, an antimitotic agent, a toxin, a radioactive isotope, a toxin, a therapeutic agent, or a combination thereof. In one embodiment, the therapeutic agent comprises an antibody, a chemotherapy agent, an enzyme, or a combination thereof.

In another aspect, the application provides pharmaceutical compositions. In one embodiment, the pharmaceutical composition includes the antibodies or antigen-binding fragments thereof and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition includes the immuno-conjugate disclosed herein and a pharmaceutically acceptable carrier.

The antibodies and antigen-binding fragments or immuno-conjugates can be prepared in a physiologically acceptable formulation and may comprise a pharmaceutically acceptable carrier, diluent and/or excipient using known techniques. For example, the antibody disclosed herein may include any functionally equivalent antibody or functional parts thereof, in particular, the monoclonal antibody including any functionally equivalent antibody or functional parts thereof is combined with a pharmaceutically acceptable carrier, diluent and/or excipient to form a therapeutic composition. Suitable pharmaceutical carriers, diluents and/or excipients are well known in the art and include, for example, phosphate buffered saline solutions, water, emulsions such as oil/water emulsions.

The pharmaceutical composition may further comprise proteinaceous carriers such as, for example, serum albumin or immunoglobulin, particularly of human origin. In one embodiment, the proteinaceous pharmaceutically active matter may be present in amounts between 1 ng and 10 mg per dose. Generally, the regime of administration should be in the range of between 0.1 μg and 10 mg of the antibody according to the disclosure, particularly in a range 1.0 μg to 1.0 mg, and more particularly in a range of between 1.0 μg and 100 μg, with all individual numbers falling within these ranges also being part of the disclosure. If the administration occurs through continuous infusion a more proper dosage may be in the range of between 0.01 μg and 10 mg units per kilogram of body weight per hour with all individual numbers falling within these ranges also being part of the disclosure.

“Pharmaceutically acceptable” refers to those compounds, materials, compositions, and dosage forms which are, within the scope of sound medical judgment, suitable for use contact with the tissues of human beings or animals without excessive toxicity, irritation, or other problem or complication, commensurate with a reasonable benefit/risk ratio. Formulation of the pharmaceutical composition according to the disclosure can be accomplished according to standard methodology know to those of ordinary skill in the art.

Further biologically active agents may be present in the pharmaceutical composition of the disclosure dependent on the intended use. In one embodiment, the composition disclosed herein may be administered in combination with other compositions comprising a biologically active/therapeutical substance or compound, particularly at least one compound selected from the group consisting of the therapeutic agent comprises capecitabine, cisplatin, trastuzumab, fulvestrant, tamoxifen, letrozole, exemestane, anastrozole, aminoglutethimide, testolactone, vorozole, formestane, fadrozole, letrozole, erlotinib, lafatinib, dasatinib, gefitinib, imatinib, pazopinib, lapatinib, sunitinib, nilotinib, sorafenib, nab-palitaxel, calicheamicin, antimitotic agent, monomethyl auristatin E, emtansine, ozogamicin, a derivative or a combination thereof.

In another aspect, the application provides methods for treating a subject using anti-ROR1 antibodies or other molecules containing the antigen-binding portion of an anti-ROR1 antibody. In one embodiment, the method inhibits growth of tumour cells. In some embodiments, the method uses the disclosed antibodies or compositions to stimulate a protective autoimmune response, to modify an immune response or to stimulate antigen-specific immune responses.

In one embodiment, the method include the step of administering to a subject in need of such treatment an effective amount of the anti-ROR1 antibodies or other molecules or composition disclosed herein.

The compositions may be administered to a subject in the form of a solid, liquid or aerosol at a suitable, pharmaceutically effective dose. Examples of solid compositions include pills, creams, and implantable dosage units. Pills may be administered orally. Therapeutic creams may be administered topically. Implantable dosage units may be administered locally, for example, at a tumour site, or may be implanted for systematic release of the therapeutic composition, for example, subcutaneously. Examples of liquid compositions include formulations adapted for injection intramuscularly, subcutaneously, intravenously, intra-arterially, and formulations for topical and intraocular administration. Examples of aerosol formulations include inhaler formulations for administration to the lungs.

The compositions may be administered by standard routes of administration. In general, the composition may be administered by topical, oral, rectal, nasal, interdermal, intraperitoneal, or parenteral (for example, intravenous, subcutaneous, or intramuscular) routes. In addition, the composition may be incorporated into sustained release matrices such as biodegradable polymers, the polymers being implanted in the vicinity of where delivery is desired, for example, at the site of a tumour. The method includes administration of a single dose, administration of repeated doses at predetermined time intervals, and sustained administration for a predetermined period of time.

In one embodiment, administration may be parenterally, e.g. intravenously. Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Non-aqueous solvents include without being limited to it, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable organic esters such as ethyl oleate. Aqueous solvents may be chosen from the group consisting of water, alcohol/aqueous solutions, emulsions or suspensions including saline and buffered media. Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils. Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose) and others. Preservatives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, inert gases, etc.

It is well known to those of ordinary skill in the art that the dosage of the composition will depend on various factors such as, for example, the condition of being treated, the particular composition used, and other clinical factors such as weight, size, sex and general health condition of the patient, body surface area, the particular compound or composition to be administered, other drugs being administered concurrently, and the route of administration.

The term “therapeutically effective amount” refers to the amount of antibody which, when administered to a human or animal, elicits a response which is sufficient to result in a therapeutic effect in said human or animal. The effective amount is readily determined by one of ordinary skill in the art following routine procedures.

Varieties of cancer may be treated using the disclosed mAb, antigen-binding fragments, or compositions. Cancers, including breast cancer, colorectal cancer, pancreatic cancer, head and neck cancer, melanoma, ovarian cancer, prostate cancer, non-small lung cell cancer, glioma, esophageal cancer, nasopharyngeal cancer, anal cancer, rectal cancer, gastric cancer, bladder cancer, cervical cancer, or brain cancer, may express ROR1 genes. In one embodiment, administering a therapeutically effective amount of composition comprising anti-ROR1 monoclonal antibodies or antigen-binding fragment or its immuno-conjugates thereof is used to cure, prevent, ameliorate, and delay the development or metastasis of cancers.

The present disclosure may be understood more readily by reference to the following detailed description of specific embodiments included herein. Although the present disclosure has been described with reference to specific details of certain embodiments thereof, it is not intended that such details should be regarded as limitations upon the scope of the disclosure.

EXAMPLES Example 1: Generation of Anti-ROR1 Antibodies

Monoclonal antibodies against human ROR1 were developed by immunizing New Zealand white rabbits. As shown in FIG. 1 , animals were immunized with recombinant human or mouse ROR1 extracellular domain (ECD) or HEK 293 cells transiently transfected with mouse or human ROR1 mixed 1:1 v/v with Complete or incomplete Freund's adjuvant (Cohort 1) or Titermax Gold (Cohort 2) alternating with Alhydrogel 2% (Alum) plus CpG 2007 and were performed by subcutaneous injection. Subsequent boosts were performed at days 7, 14, 21, 28 and 37 as shown in FIG. 2 .

On week 5 the serum from the animals was tested for ROR1 titer by ELISA. Serum from each rabbit is obtained before immunization as a negative control. After immunization serum is again collected from each animal and compared to the pre-immunization serum from the same animal for the presence of ROR1-specific IgG antibodies. As shown in FIG. 6 all animals immunized with human and mouse ROR1 developed detectable titres of human or mouse ROR1-specific IgG antibodies.

As shown in FIG. 3 , spleen and lymph nodes were harvest from 2 animals each on days 4, 13, and 21 following a final immunization. ROR1-specific IgG+B cells were sorted at 1 per well into multiple 96 well tissue culture plates and cultured for 9 days to allow their differentiation into plasma cells and for secretion of antibodies. The supernatants from these plasma cell cultures were screened by ELISA and flow cytometry for the presence of ROR1-specific antibodies in a series of binding assays as listed below:

Human ROR1 directly coated on the plate—detection of ROR1-specific IgG ELISA

Mouse ROR1 directly coated on the plate—detection of ROR1-specific IgG ELISA

Human ROR2 directly coated on the plate—detection of ROR1-specific IgG ELISA

Biotinylated human ROR1 added to an avidin coated plate—detection of ROR1-specific IgG ELISA

Biotinylated human ROR1 “Kringle domain” added to an avidin coated plate—detection of ROR1-Kringle-specific IgG ELISA

Biotinylated human ROR1 “Frizzled-Kringle domain” added to an avidin coated plate—detection of ROR1-Frizzled-Kringle-specific IgG ELISA

Biotinylated human ROR1 “Ig-Frizzled domain” added to an avidin coated plate—detection of ROR1-Ig-Frizzled-specific IgG ELISA

Human ROR1 “Frizzled-Kringle domain” directly coated on the plate—detection of ROR1-Frizzled-Kringle-specific IgG ELISA

Human ROR1 “Ig-Frizzled domain” directly coated on the plate—detection of ROR1-Ig-Frizzled-specific IgG ELISA

Human ROR1-CHO cells—detection of ROR1-specific IgG by FACS

On day 9 of B cell culture the supernatants were separated from the B cells and stored in a separate plate for later analysis. RNA later tissue storage reagent was added to each well in the B cell culture plate to preserve the RNA in the B cells for RT-PCR amplification of antibody variable regions.

B cell culture wells identified through ELISA and FACS screening as having the desired antibodies we advanced to molecular “rescue” of the antibody variable regions. The light and heavy chain variable sequences were amplified by multiplex RT-PCR using degenerate primers designed to anneal to leader sequences and the constant regions of rabbit IgG and rabbit kappa sequences. Secondary PCR was performed separately for the light and heavy chains using nested primers containing restriction sites. Amplicons from the variable heavy chain PCR were cloned into an expression vector containing human IgG1. Light chain amplicons were cloned into an expression vector containing human IgK. Resulting clones were sequenced and analyzed.

The heavy and light chain expression plasmids generated from each well were transiently co-transfected to produce rabbit/human chimeric antibodies. Recombinant antibody supernatants were confirmed to contain anti-ROR1 antibodies using bio-layer interferometry analysis on a ForteBio Octet Red 96 instrument. Anti-human Fc biosensors (Pall ForteBio) were used to capture antibodies in the supernatants. Association to ROR1 was observed by real-time interferometry by placing the biosensors in wells containing recombinant human ROR1 extracellular domain protein. Dissociation was measured after transfer of the biosensors into wells containing 10× kinetics buffer (Pall ForteBio). The software provided by the manufacturer was used to analyze the interferometry data.

A summary of the primary BCC screening data and the corresponding screening data for 27 recombinant chimeric rabbit/human IgG antibodies is shown in Tables 4a and 4b.

The heavy and light chain variable regions for 8 of 27 chimeric rabbit/human IgG antibodies listed in FIG. 4 were humanized. Humanized variants for 8 of 27 antibodies showed similar binding kinetics to human ROR1 by octet analysis which is summarized in FIG. 5 .

While the disclosure has been particularly shown and described as referenced to the embodiments thereof, those skilled in the art will understand that the foregoing and other changes in form and detail may be made therein without departing from the spirit and scope. All references cited or referred to in this disclosure are hereby incorporated by reference in their entireties.

SEQUENCE LISTING ANTI-ROR1 ANTIBODY SEQUENCES 226E12 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 1 GCCTATGATATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGG GCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATG TTCGGCGGAGGGACCGAGGTGGTGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 226E12 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 2 GCCTATGATATGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGG GCATCCACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTACACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATG TTCGGCGGAGGGACCGAGGTGGTGGTCAAA 226E12 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 3 AYDMTQTPSSVSAAVGGTVTIKCQASQRIYSYLAWYQQKPGQPPKLLIYRASTLASGVPSRFKGSGSGTEYTLTI SDLECADAATYYCQQGASMVDVENMFGGGTEVVVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 226E12 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 4 AYDMTQTPSSVSAAVGGTVTIKCQASQRIYSYLAWYQQKPGQPPKLLIYRASTLASGVPSRFKGSGSGTEYTLTI SDLECADAATYYCQQGASMVDVENMFGGGTEVVVK 226E12 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 5 CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGAA TTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAGTGGATCGGAGCCATT AATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACC ACGGTGGATCTGAAGATCACCAGTCCGACAATTGAGGACACGGCCACCTATTTCTGTGCCAGAAGTGTGAGTAAT AATTTCGCCGAATATAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCG GTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTAC TTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTA CAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATC TGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCAC ACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGAC ACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAG TTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACG TACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCC AACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAC ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCA TGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 226E12 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 6 CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGAA TTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAGTGGATCGGAGCCATT AATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACC ACGGTGGATCTGAAGATCACCAGTCCGACAATTGAGGACACGGCCACCTATTTCTGTGCCAGAAGTGTGAGTAAT AATTTCGCCGAATATAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGC 226E12 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 7 QSLEESGGRLVTPGTPLTLTCTASEFSLSNYYMSWVRQAPGEGLEWIGAINADSDNTWYPSWVKGRFTISKTSST TVDLKITSPTIEDTATYFCARSVSNNFAEYNIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTH TCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 226E12 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 8 QSLEESGGRLVTPGTPLTLTCTASEFSLSNYYMSWVRQAPGEGLEWIGAINADSDNTWYPSWVKGRFTISKTSST TVDLKITSPTIEDTATYFCARSVSNNFAEYNIWGPGTLVTVSS 323H7 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 9 CAAGCCGTGGTGACCCAGACTCCATCGTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCC AGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATC TACTATGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTC GCCATCAGCGACCTGGAGTGTGACGATTCTGCCACTTACTACTGTGCAGGCGGTTATGATACGGATGGTCTTGAT ACGTTTGCTTTCGGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCG CCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCC AAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGC GAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 323H7 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 10 CAAGCCGTGGTGACCCAGACTCCATCGTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAGTTGCCAGTCC AGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATC TACTATGCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTC GCCATCAGCGACCTGGAGTGTGACGATTCTGCCACTTACTACTGTGCAGGCGGTTATGATACGGATGGTCTTGAT ACGTTTGCTTTCGGCGGAGGCACCGAGGTGGAGGTCAAA 323H7 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 11 QAVVTQTPSSVSAAVGGTVTISCQSSQSVYNNNDLAWYQQKPGQPPKLLIYYASTLASGVSSRFKGSGSGTQFTL AISDLECDDSATYYCAGGYDTDGLDTFAFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 323H7 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 12 QAVVTQTPSSVSAAVGGTVTISCQSSQSVYNNNDLAWYQQKPGQPPKLLIYYASTLASGVSSRFKGSGSGTQFTL AISDLECDDSATYYCAGGYDTDGLDTFAFGGGTEVEVK 323H7 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 13 CAGGAGCAGCTGAAGGAGTCCGGAGGAGGCCTGGTAACGCCTGGAGGAACCCTGACACTCACCTGCACAGCCTCT GGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGTCAT ATTTATGTTAATAATGATGACACAGACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACC ACGGTGGATCTGAAGATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATTGGATGTTGGT GGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGC CCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACC TACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAA ACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCC AAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG GTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 323H7 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 14 CAGGAGCAGCTGAAGGAGTCCGGAGGAGGCCTGGTAACGCCTGGAGGAACCCTGACACTCACCTGCACAGCCTCT GGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGTCAT ATTTATGTTAATAATGATGACACAGACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACC ACGGTGGATCTGAAGATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATTGGATGTTGGT GGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAAGGGACCCTGGTCACCGTCTCGAGC 323H7 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 15 QEQLKESGGGLVTPGGTLTLTCTASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASWAKGRFTISKTST TVDLKITSPTTEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 323H7 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 16 QEQLKESGGGLVTPGGTLTLTCTASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASWAKGRFTISKTST TVDLKITSPTTEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSS 324C7 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 17 GACATTGTGATGACCCAGACTCCAGCCTCTGTGGAGGTCGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACT ACATCCAATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGGTTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCAGTTACTGCTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGG AATGCTTTCGGCGGAGGCACCGAGGTGGTGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324C7 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 18 GACATTGTGATGACCCAGACTCCAGCCTCTGTGGAGGTCGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTATACT ACATCCAATCTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGGTTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCAGTTACTGCTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGG AATGCTTTCGGCGGAGGCACCGAGGTGGTGGTCAAA 324C7 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 19 DIVMTQTPASVEVAVGGTVTIKCQASQNIGSDLAWYQQKPGQPPKLLIYTTSNLASGVPSRFKGSGSGTGFTLTI SDLECADAASYCCQGGYFSGRNIYGNAFGGGTEVVVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324C7 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 20 DIVMTQTPASVEVAVGGTVTIKCQASQNIGSDLAWYQQKPGQPPKLLIYTTSNLASGVPSRFKGSGSGTGFTLTI SDLECADAASYCCQGGYFSGRNIYGNAFGGGTEVVVK 324C7 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 21 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGA TTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATACATT GATAGTGGTGCTACCACATACTACGCGAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAGCCTCGACCACGGTG GATCTGAAAATCGCCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGATACTACGGCATGGAC CCCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACG GTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCA GCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGAC GGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGG GATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC CTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324C7 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 22 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGA TTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGATACATT GATAGTGGTGCTACCACATACTACGCGAGCTGGGCAAAAGGCCGATTCACCATCTCCAAAGCCTCGACCACGGTG GATCTGAAAATCGCCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGGATACTACGGCATGGAC CCCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGC 324C7 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 23 QSVEESGGRLVTPGTPLTLTCTVSGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASWAKGRFTISKASTTV DLKIASPTTEDTATYFCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP APEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324C7 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 24 QSVEESGGRLVTPGTPLTLTCTVSGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASWAKGRFTISKASTTV DLKIASPTTEDTATYFCARGYYGMDPWGQGTLVTVSS 323D10 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 25 GCCATCGATTTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCATCAATTGCCAAGCC AGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACGAA ACATCCAAACTGGCATCTGGGGTCCCACCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATC AGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAGTTATTATCGTATTAATAATATTGGTTACGAT AATGCTTTCGGCGGAGGCACCGAGGTGGAGTTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 323D10 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 26 GCCATCGATTTGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAATCACCATCAATTGCCAAGCC AGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGCAGCGTCCCAAGCTCCTGATCTACGAA ACATCCAAACTGGCATCTGGGGTCCCACCGCGGTTCAGCGGCAGTGGATCTGGGACACAGTTCACTCTCACCATC AGCGGCGTGCAGTGTGACGATGCTGCCACTTACTACTGTCAAAGTTATTATCGTATTAATAATATTGGTTACGAT AATGCTTTCGGCGGAGGCACCGAGGTGGAGTTCAAA 323D10 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 27 AIDLTQTPASVEAAVGGTITINCQASESISSWLAWYQQKPGQRPKLLIYETSKLASGVPPRFSGSGSGTQFTLTI SGVQCDDAATYYCQSYYRINNIGYDNAFGGGTEVEFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 323D10 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 28 AIDLTQTPASVEAAVGGTITINCQASESISSWLAWYQQKPGQRPKLLIYETSKLASGVPPRFSGSGSGTQFTLTI SGVQCDDAATYYCQSYYRINNIGYDNAFGGGTEVEFK 323D10 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 29 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGATACATT AGCACTAGTGGTACCACATTCTACGCGAACTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGACTATAACTACGCCATG GACATCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCA CCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTG ACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTC TACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCAC AAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGC CCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCC CGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCA GCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC CGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCAT GAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 323D10 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 30 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGATACATT AGCACTAGTGGTACCACATTCTACGCGAACTGGGTGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAGACTATAACTACGCCATG GACATCTGGGGCCAAGGCACCCTGGTCACCGTCTCGAGC 323D10 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 31 QSVEESGGRLVTPGTPLTLTCTVSGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANWVKGRFTISKTSTTV DLKMTSLTTEDTATYFCARDYNYAMDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPV TVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPC PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS VLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 323D10 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 32 QSVEESGGRLVTPGTPLTLTCTVSGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANWVKGRFTISKTSTTV DLKMTSLTTEDTATYFCARDYNYAMDIWGQGTLVTVSS 324E2 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 33 GCTCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGTCC AGTCAGAGTGTTAATAACAACGACTTAGCCTGGTTTCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTAC TGGGCATCCAAACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCATTCTCACC ATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTC GGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAG CAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGG AAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324E2 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 34 GCTCAAGTGCTGACCCAGACTCCATCCTCCGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGTCC AGTCAGAGTGTTAATAACAACGACTTAGCCTGGTTTCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTAC TGGGCATCCAAACTGGCATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCATTCTCACC ATCAGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTC GGCGGAGGCACCGAGGTGGAGGTCAAA 324E2 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 35 AQVLTQTPSSVSAAVGGTVTINCQSSQSVNNNDLAWFQQKPGQPPKRLIYWASKLASGVPSRFKGSGSGTQFILT ISDLECDDAATYYCAGGYSGNIYGFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324E2 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 36 AQVLTQTPSSVSAAVGGTVTINCQSSQSVNNNDLAWFQQKPGQPPKRLIYWASKLASGVPSRFKGSGSGTQFILT ISDLECDDAATYYCAGGYSGNIYGFGGGTEVEVK 324E2 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 37 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGAATCATT AGTAGTAGTGGTACCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACG GTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCGGAGCATTTAGCGTCTGG GGCCCGGGCACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCC AAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCG TGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTC AGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCT GAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCT GAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATC GAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAG CTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAG AGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTAT AGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTG CACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324E2 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 38 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAATACATCGGAATCATT AGTAGTAGTGGTACCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGTCGACCACG GTGGATCTGAAAATGACCAGTCTGACAACCGAGGACACGGCCACCTATTTCTGTGCCGGAGCATTTAGCGTCTGG GGCCCGGGCACCCTCGTCACCGTCTCGAGC 324E2 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 39 QSVEESGGRLVTPGTPLTLTCTVSGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASWAKGRFTISKTSSTT VDLKMTSLTTEDTATYFCAGAFSVWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAP EAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324E2 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 40 QSVEESGGRLVTPGTPLTLTCTVSGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASWAKGRFTISKTSSTT VDLKMTSLTTEDTATYFCAGAFSVWGPGTLVTVSS 324C6 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 41 GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAACAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACCAG GCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGCGCTTATGGTGTTAGTGGTACTAGTAGTTAT TTATATACTTTCGGCGGAGGCACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCG CCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCC AAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGC GAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324C6 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 42 GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAACAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACCAG GCATCCACTCTGGCATCTGGGGTCTCATCGCGGTTCAAAGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTACTGTCAATGCGCTTATGGTGTTAGTGGTACTAGTAGTTAT TTATATACTTTCGGCGGAGGCACCGAGGTGGAGGTCAAA 324C6 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 43 DVVMTQTPASVEAAVGGTVTIKCQASQSIDSWLSWYQQKPGQPPKLLIYQASTLASGVSSRFKGSGSGTEFTLTI SDLECADAATYYCQCAYGVSGTSSYLYTFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324C6 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 44 DVVMTQTPASVEAAVGGTVTIKCQASQSIDSWLSWYQQKPGQPPKLLIYQASTLASGVSSRFKGSGSGTEFTLTI SDLECADAATYYCQCAYGVSGTSSYLYTFGGGTEVEVK 324C6 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 45 CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGGA TTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATTGGAACCATT TATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATCACTAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATCCTATTATGGCGGTGAT AAGACTGGTTTAGGCATCTGGGGCCCAGGCACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTC TTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTC CCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGC AACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAAC AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324C6 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 46 CAGTCGCTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGCCTCTGGA TTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATTGGAACCATT TATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATCACTAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATCCTATTATGGCGGTGAT AAGACTGGTTTAGGCATCTGGGGCCCAGGCACCCTCGTCACCGTCTCGAGC 324C6 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 47 QSLEESGGRLVTPGTPLTLTCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKTSTTV DLKITSPTTEDTATYFCARSYYGGDKTGLGIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324C6 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 48 QSLEESGGRLVTPGTPLTLTCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKTSTTV DLKITSPTTEDTATYFCARSYYGGDKTGLGIWGPGTLVTVSS 338H4 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 49 GACATTGTGATGACCCAGACTCCAGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCC AGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTATCTG GCATCTACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAAGCAGTGGATCTGGGACAGAGTACACTCTCACCATC AGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGA GGGACCGAGGTGGAGGTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTG AAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTG GATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 338H4 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 50 GACATTGTGATGACCCAGACTCCAGCCTCGGTGTCTGCAGCTGTGGGAGGCACAGTCACCATCAATTGCCAGGCC AGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCGCCTGATCTATCTG GCATCTACTCTGGCATCTGGGGTCCCATCGCGGTTCAAAAGCAGTGGATCTGGGACAGAGTACACTCTCACCATC AGCGACCTGGAGTGTGACGATGCTGCCACTTACTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGA GGGACCGAGGTGGAGGTCAAA 338H4 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 51 DIVMTQTPASVSAAVGGTVTINCQASQNIYSYLSWYQQKPGQPPKRLIYLASTLASGVPSRFKSSGSGTEYTLTI SDLECDDAATYYCQSNYNGNYGFGGGTEVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 338H4 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 52 DIVMTQTPASVSAAVGGTVTINCQASQNIYSYLSWYQQKPGQPPKRLIYLASTLASGVPSRFKSSGSGTEYTLTI SDLECDDAATYYCQSNYNGNYGFGGGTEVEVK 338H4 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 53 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAATGGATCGGAATCATT TATGCTAGTGGTAGCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAATTTATGACGGCATGGAC CTCTGGGGCCCAGGGACCCTCGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCC TCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACG GTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTAC TCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAG CCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCA GCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGG ACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGAC GGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTC CTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCC CCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGG GATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTC CTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAG GCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 338H4 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 54 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACCGTCTCTGGA TTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAATGGATCGGAATCATT TATGCTAGTGGTAGCACATACTACGCGAGCTGGGCGAAAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAAAATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGAATTTATGACGGCATGGAC CTCTGGGGCCCAGGGACCCTCGTCACCGTCTCGAGC 338H4 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 55 QSVEESGGRLVTPGTPLTLTCTVSGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASWAKGRFTISKTSTTV DLKITSPTTEDTATYFCARIYDGMDLWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCP APEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 338H4 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 56 QSVEESGGRLVTPGTPLTLTCTVSGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASWAKGRFTISKTSTTV DLKITSPTTEDTATYFCARIYDGMDLWGPGTLVTVSS 330F11 CHIMERIC LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 57 GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGG GCATCCACTCTGGAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTATTGTCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGC GGAGGGACCGAGGTGGAGTTCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAG TTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAG GTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAG GGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 330F11 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 58 GATGTTGTGATGACCCAGACTCCAGCCTCCGTGGAGGCAGCTGTGGGAGGCACAGTCACCATCAAGTGCCAGGCC AGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGCAGCCTCCCAAGCTCCTGATCTACAGG GCATCCACTCTGGAATCTGGGGTCCCATCGCGGTTCAAAGGCAGTGGATCTGGGACACAGTTCACTCTCACCATC AGCGACCTGGAGTGTGCCGATGCTGCCACTTACTATTGTCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGC GGAGGGACCGAGGTGGAGTTCAAA 330F11 CHIMERIC LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED SEQ ID NO: 59 DVVMTQTPASVEAAVGGTVTIKCQASQSINNYLAWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTQFTLTI SDLECADAATYYCQSYNGVGRTAFGGGTEVEFKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 330F11 CHIMERIC LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 60 DVVMTQTPASVEAAVGGTVTIKCQASQSINNYLAWYQQKPGQPPKLLIYRASTLESGVPSRFKGSGSGTQFTLTI SDLECADAATYYCQSYNGVGRTAFGGGTEVEFK 330F11 CHIMERIC HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 61 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGA TTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAATGGATCGGAACCATT AGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAGCATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATATTCTTCTACTACTGAT TGGACCTACTTTAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTC TTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTC CCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAG TCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGC AACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACC CTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTC AACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAAC AAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACC CTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGC GACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCC GACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 330F11 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 62 CAGTCGGTGGAGGAGTCCGGGGGTCGCCTGGTCACGCCTGGGACACCCCTGACACTCACCTGCACAGTCTCTGGA TTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGGAGGGGCTGGAATGGATCGGAACCATT AGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCCGATTCACCATCTCCAAAACCTCGACCACGGTG GATCTGAGCATCACCAGTCCGACAACCGAGGACACGGCCACCTATTTCTGTGCCAGATATTCTTCTACTACTGAT TGGACCTACTTTAACATCTGGGGCCCGGGCACCCTGGTCACCGTCTCGAGC 330F11 CHIMERIC HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 63 QSVEESGGRLVTPGTPLTLTCTVSGFSLNNYWMSWVRQAPGEGLEWIGTISSGAYTWFATWATGRFTISKTSTTV DLSITSPTTEDTATYFCARYSSTTDWTYFNIWGPGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHT CPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTY RVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 330F11 CHIMERIC HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 64 QSVEESGGRLVTPGTPLTLTCTVSGFSLNNYWMSWVRQAPGEGLEWIGTISSGAYTWFATWATGRFTISKTSTTV DLSITSPTTEDTATYFCARYSSTTDWTYFNIWGPGTLVTVSS 226E12 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 65 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATAGG GCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATC AGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATG TTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGAT GAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAG TGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACC TACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACC CATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 226E12 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 66 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGAATTTACAGCTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATCTATAGG GCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATC AGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAACAGGGTGCTAGTATGGTTGATGTTGAGAATATG TTCGGCGGAGGGACCAAGGTGGAGATCAAA 226E12 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 67 DIQMTQSPSSLSASVGDRVTITCQASQRIYSYLAWYQQKPGKVPKLLIYRASTLASGVPSRFSGSGSGTDFTLTI SSLQPEDVATYYCQQGASMVDVENMFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQ WKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 226E12 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 68 DIQMTQSPSSLSASVGDRVTITCQASQRIYSYLAWYQQKPGKVPKLLIYRASTLASGVPSRFSGSGSGTDFTLTI SSLQPEDVATYYCQQGASMVDVENMFGGGTKVEIK 226E12 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 69 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGCC ATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGGTTCACCATCTCCAGAGACAATTCC AAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAAGTGTG AGTAATAATTTCGCCGAATATAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGC CCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACC TACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAA ACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCC AAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG GTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 226E12 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 70 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAGTAACTACTACATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGCC ATTAATGCTGACAGTGATAATACATGGTACCCGAGCTGGGTGAAAGGCCGGTTCACCATCTCCAGAGACAATTCC AAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGAAGTGTG AGTAATAATTTCGCCGAATATAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 226E12 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 71 EVQLLESGGGLVQPGGSLRLSCAASGFSLSNYYMSWVRQAPGKGLEWIGAINADSDNTWYPSWVKGRFTISRDNS KNTLYLQMNSLRAEDTAVYYCARSVSNNFAEYNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 226E12 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 72 EVQLLESGGGLVQPGGSLRLSCAASGFSLSNYYMSWVRQAPGKGLEWIGAINADSDNTWYPSWVKGRFTISRDNS KNTLYLQMNSLRAEDTAVYYCARSVSNNFAEYNIWGQGTLVTVSS 323H7 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 73 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCC AGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATC TATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTC ACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATGATACGGATGGTCTTGAT ACGTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCG CCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCC AAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGC GAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 323H7 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 74 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCC AGTCAGAGTGTTTATAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCTCCTGATC TATTATGCATCCACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTTCACTCTC ACCATCAGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTGCAGGCGGTTATGATACGGATGGTCTTGAT ACGTTTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA 323H7 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 75 DIQMTQSPSSLSASVGDRVTITCQSSQSVYNNNDLAWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTL TISSLQPEDVATYYCAGGYDTDGLDTFAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 323H7 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 76 DIQMTQSPSSLSASVGDRVTITCQSSQSVYNNNDLAWYQQKPGKVPKLLIYYASTLASGVPSRFSGSGSGTDFTL TISSLQPEDVATYYCAGGYDTDGLDTFAFGGGTKVEIK 323H7 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 77 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGACAT ATTTATGTTAATAATGATGACACAGACTACGCGAGCTCCGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCC AAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCACCTATTTCTGTGCGAGATTGGAT GTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACC AAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTG GTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTC CCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGT GACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCA AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGAC CCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAG TACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAG TGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAA CCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAA GGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGG AACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCG GGT 323H7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 78 GAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCACCATCAGTCGCTACCACATGACTTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGACAT ATTTATGTTAATAATGATGACACAGACTACGCGAGCTCCGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCC AAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCACCTATTTCTGTGCGAGATTGGAT GTTGGTGGTGGTGGTGCTTATATTGGGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 323H7 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 79 EVQLLESGGGLVQPGGSLRLSCAASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASSAKGRFTISRDNS KNTLYLQMNSLRAEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCL VKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSC DKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSP G 323H7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED SEQ ID NO: 80 EVQLLESGGGLVQPGGSLRLSCAASGFTISRYHMTWVRQAPGKGLEWIGHIYVNNDDTDYASSAKGRFTISRDNS KNTLYLQMNSLRAEDTATYFCARLDVGGGGAYIGDIWGQGTLVTVSS 324C7 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 81 GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCAGGCC AGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATACT ACATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATC AGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGG AATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324C7 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 82 GACATCCAGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGTCAGGCC AGTCAGAACATTGGTAGTGATTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATACT ACATCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATC AGCAGCCTGCAGCCTGAAGATTTTGCAACTTACTATTGTCAAGGCGGTTATTTTAGTGGTCGTAATATTTATGGG AATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA 324C7 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 83 DIQMTQSPSSVSASVGDRVTITCQASQNIGSDLAWYQQKPGKAPKLLIYTTSNLASGVPSRFSGSGSGTDFTLTI SSLQPEDFATYYCQGGYFSGRNIYGNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324C7 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 84 DIQMTQSPSSVSASVGDRVTITCQASQNIGSDLAWYQQKPGKAPKLLIYTTSNLASGVPSRFSGSGSGTDFTLTI SSLQPEDFATYYCQGGYFSGRNIYGNAFGGGTKVEIK 324C7 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE - VARIANT 1 SEQ ID NO: 85 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTAC ATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAG AACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTAC GGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCC CTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG ATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324C7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE - VARIANT 1  SEQ ID NO: 86 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTAC ATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAG AACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTAC GGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 324C7 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE - VARIANT 1. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 87 EVQLVESGGGLVQPGGSLRLSCAASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324C7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE - VARIANT 1. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 88 EVQLVESGGGLVQPGGSLRLSCAASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSS 324C7 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE - VARIANT 2 SEQ ID NO: 89 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCT GGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTAC ATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAAAGACAATGCCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTAC GGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCC CTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG ATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324C7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE - VARIANT 2 SEQ ID NO: 90 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCT GGATTCTCCCTCAGTGGCGCTGGAGTGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGGTAC ATTGATAGTGGTGCTACCACATACTACGCGAGCAGTGCAAAAGGCAGATTCACCATCTCCAAAGACAATGCCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGGATACTAC GGCATGGACCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 324C7 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE - VARIANT 2. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 91 EVQLVESGGGLVQPGGSLRLSCTASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISKDNAK NTVDLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324C7 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE - VARIANT 2. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 92 EVQLVESGGGLVQPGGSLRLSCTASGFSLSGAGVSWVRQAPGKGLEWIGYIDSGATTYYASSAKGRFTISKDNAK NTVDLQMNSLRAEDTAVYYCARGYYGMDPWGQGTLVTVSS 323D10 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 93 GCCATCGATTTGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGGCACAATCACCATCAATTGCCAAGCC AGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAA ACATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGTTATTATCGTATTAATAATATTGGTTACGAT AATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAA GTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAA GTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 323D10 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 94 GCCATCGATTTGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGGCACAATCACCATCAATTGCCAAGCC AGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAA ACATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGTTATTATCGTATTAATAATATTGGTTACGAT AATGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA 323D10 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 95 AIDLTQSPSTLSASVGGTITINCQASESISSWLAWYQQKPGKAPKLLIYETSKLASGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSYYRINNIGYDNAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAK VQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 323D10 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 96 AIDLTQSPSTLSASVGGTITINCQASESISSWLAWYQQKPGKAPKLLIYETSKLASGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSYYRINNIGYDNAFGGGTKVEIK 323D10 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 97 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCT GGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGATAC ATTAGCACTAGTGGTACCACATTCTACGCGAACAGCGTGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTATAAC TACGCCATGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTC CCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCC GAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCC TCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAAC GTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGC CCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTC ATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAAC TGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGT GTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAA GCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTG CCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGAC GGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCC GTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 323D10 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 98 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCT GGATTCTCCCTCAGTAGGAATGCAATGAACTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGATAC ATTAGCACTAGTGGTACCACATTCTACGCGAACAGCGTGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTATAAC TACGCCATGGACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 323D10 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 99 EVQLVESGGGLVQPGGSLRLSCTASGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANSVKGRFTISKDNTK NTVDLQMNSLRAEDTAVYYCARDYNYAMDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTC PPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 323D10 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 100 EVQLVESGGGLVQPGGSLRLSCTASGFSLSRNAMNWVRQAPGKGLEYIGYISTSGTTFYANSVKGRFTISKDNTK NTVDLQMNSLRAEDTAVYYCARDYNYAMDIWGQGTLVTVSS 324E2 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 101 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCC AGTCAGAGTGTTAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTAT TGGGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACA ATCAGCAACCTGCAGCCTGAAGATTTTGCAACTTATTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTC GGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAG CAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGG AAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTAC AGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324E2 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 102 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGTCC AGTCAGAGTGTTAACAACAACGACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCGCCTGATCTAT TGGGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACA ATCAGCAACCTGCAGCCTGAAGATTTTGCAACTTATTACTGTGCAGGCGGTTATAGTGGTAATATTTATGGTTTC GGCGGAGGGACCAAGGTGGAGATCAAA 324E2 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 103 DIQMTQSPSSLSASVGDRVTITCQSSQSVNNNDLAWYQQKPGKAPKRLIYWASKLASGVPSRFSGSGSGTEFTLT ISNLQPEDFATYYCAGGYSGNIYGFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQW KVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324E2 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 104 DIQMTQSPSSLSASVGDRVTITCQSSQSVNNNDLAWYQQKPGKAPKRLIYWASKLASGVPSRFSGSGSGTEFTLT ISNLQPEDFATYYCAGGYSGNIYGFGGGTKVE1K 324E2 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 105 CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGA TTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAATCATT AGTAGTAGTGGTACCACATACTACGCGAGCTCCGCGAAAGGCAGATTCACCATCTCCAAAGACACCTCCAAGAAC ACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGGGAGCATTTAGCGTC TGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCC TCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTG TCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCC CTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCC AGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCA CCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACC CCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTC ACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCC ATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAT GAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGG GAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTC TATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCT CTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324E2 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 106 CAGTCGGTGGAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACCGCCTCTGGA TTCTCCCTCAGTAACAATGCAATAACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAATCATT AGTAGTAGTGGTACCACATACTACGCGAGCTCCGCGAAAGGCAGATTCACCATCTCCAAAGACACCTCCAAGAAC ACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGGGAGCATTTAGCGTC TGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 324E2 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 107 QSVEESGGGLVQPGGSLRLSCTASGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASSAKGRFTISKDTSKN TVDLQMNSLRAEDTAVYYCAGAFSVWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTV SWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPA PEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVL TVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324E2 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 108 QSVEESGGGLVQPGGSLRLSCTASGFSLSNNAITWVRQAPGKGLEYIGIISSSGTTYYASSAKGRFTISKDTSKN TVDLQMNSLRAEDTAVYYCAGAFSVWGQGTLVTVSS 324C6 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 109 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCAG GCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTGCTTATGGTGTTAGTGGTACTAGTAGTTAT TTATATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCG CCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCC AAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAG GACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGC GAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 324C6 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE SEQ ID NO: 110 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGCATTGATAGTTGGTTATCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATCAG GCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAATCTGCTTATGGTGTTAGTGGTACTAGTAGTTAT TTATATACTTTCGGCGGAGGGACCAAGGTGGAGATCAAA 324C6 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 111 DIQMTQSPSTLSASVGDRVTITCQASQSIDSWLSWYQQKPGKAPKLLIYQASTLASGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSAYGVSGTSSYLYTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 324C6 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 112 DIQMTQSPSTLSASVGDRVTITCQASQSIDSWLSWYQQKPGKAPKLLIYQASTLASGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSAYGVSGTSSYLYTFGGGTKVE1K 324C6 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 113 CAGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGA TTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATT TATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAAC ACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCCTATTATGGC GGTGATAAGACTGGTTTAGGCATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCA TCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGAC TACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTC CTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTAC ATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACT CACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAG GACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTC AAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGC ACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTC TCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG TACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTAT CCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTC TCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 324C6 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 114 CAGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCTGGA TTCTCCCTCAGTAGGTACTACATGACCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACCATT TATACTAGTGGTAGTACATGGTACGCGAGCTGGACAAAAGGCAGATTCACCATCTCCAAAGACAATACCAAGAAC ACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATCCTATTATGGC GGTGATAAGACTGGTTTAGGCATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 324C6 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 115 QSLVESGGGLVQPGGSLRLSCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKDNTKN TVDLQMNSLRAEDTAVYYCARSYYGGDKTGLGIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKT HTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS TYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFY PSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 324C6 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 116 QSLVESGGGLVQPGGSLRLSCTASGFSLSRYYMTWVRQAPGKGLEWIGTIYTSGSTWYASWTKGRFTISKDNTKN TVDLQMNSLRAEDTAVYYCARSYYGGDKTGLGIWGQGTLVTVSS 338H4 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 117 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAGGCC AGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCGCCTGATCTATCTG GCATCTACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTACACTCTCACCATC AGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGA GGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTG AAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTG GATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTC AGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 338H4 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 118 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAGGCC AGTCAGAACATTTACAGCTACTTATCCTGGTATCAGCAGAAACCAGGGAAAGTTCCTAAGCGCCTGATCTATCTG GCATCTACTCTGGCATCTGGGGTCCCATCTCGGTTCAGTGGCAGTGGATCTGGGACAGATTACACTCTCACCATC AGCAGCCTGCAGCCTGAAGATGTTGCAACTTATTACTGTCAAAGCAATTATAACGGTAATTATGGTTTCGGCGGA GGGACCAAGGTGGAGATCAAA 338H4 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 119 DIQMTQSPSSLSASVGDRVTINCQASQNIYSYLSWYQQKPGKVPKRLIYLASTLASGVPSRFSGSGSGTDYTLTI SSLQPEDVATYYCQSNYNGNYGFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 338H4 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 120 DIQMTQSPSSLSASVGDRVTINCQASQNIYSYLSWYQQKPGKVPKRLIYLASTLASGVPSRFSGSGSGTDYTLTI SSLQPEDVATYYCQSNYNGNYGFGGGTKVE1K 338H4 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 121 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCT GGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGATCGGAATC ATTTATGCTAGTGGTAGCACATACTACGCGAGCTCGGCGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAATTTATGAC GGCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGCCCATCGGTCTTCCCC CTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAA CCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCA GGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTG AATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCC CCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGC TCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTG ATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 338H4 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 122 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTACAGCCTCT GGATTCTCCCTCAGTAGCTATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAGGGGGCTGGAGTGGATCGGAATC ATTTATGCTAGTGGTAGCACATACTACGCGAGCTCGGCGAAAGGCAGATTCACCATCTCCAAAGACAATACCAAG AACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAATTTATGAC GGCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 338H4 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 123 EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASSAKGRFTISKDNTK NTVDLQMNSLRAEDTAVYYCARIYDGMDLWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCP PCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 338H4 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 124 EVQLVESGGGLVQPGGSLRLSCTASGFSLSSYAMSWVRQAPGRGLEWIGIIYASGSTYYASSAKGRFTISKDNTK NTVDLQMNSLRAEDTAVYYCARIYDGMDLWGQGTLVTVSS 330F11 HUMANIZED LIGHT CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE SEQ ID NO: 125 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGG GCATCCACTCTGGAATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGC GGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAG TTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAG GTGGATAACGCCCTCCAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGC CTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAG GGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT  330F11 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 126 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCC AGTCAGAGCATTAATAACTACTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAGG GCATCCACTCTGGAATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATC AGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAAGCTATAATGGTGTTGGTAGGACTGCTTTCGGC GGAGGGACCAAGGTGGAGATCAAA 330F11 HUMANIZED LIGHT CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN KAPPA CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 127 DIQMTQSPSTLSASVGDRVTITCQASQSINNYLAWYQQKPGKAPKLLIYRASTLESGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSYNGVGRTAFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWK VDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 330F11 HUMANIZED LIGHT CHAIN VARIABLE LIGHT CHAIN AMINO ACID SEQUENCE. COMPIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 128 DIQMTQSPSTLSASVGDRVTITCQASQSINNYLAWYQQKPGKAPKLLIYRASTLESGVPSRFSGSGSGTEFTLTI SSLQPDDFATYYCQSYNGVGRTAFGGGTKVEIK 330F11 HUMANIZED HEAVY CHAIN FULL-LENGTH NUCLEOTIDE SEQUENCE  SEQ ID NO: 129 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACC ATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCAGATTCACCATCTCCAGAGACAATTCCAAG AACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATATTCTTCT ACTACTGATTGGACCTACTTTAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGCTAGCACCAAGGGC CCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAG GACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCT GTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACC TACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAA ACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCC AAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG GTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTC TATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTC TTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT 330F11 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN NUCLEOTIDE SEQUENCE  SEQ ID NO: 130 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCT GGATTCTCCCTCAATAACTACTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAACC ATTAGTAGTGGTGCGTATACATGGTTCGCCACCTGGGCGACAGGCAGATTCACCATCTCCAGAGACAATTCCAAG AACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGATATTCTTCT ACTACTGATTGGACCTACTTTAACATCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGC 330F11 HUMANIZED HEAVY CHAIN FULL-LENGTH AMINO ACID SEQUENCE. HUMAN GAMMA-1 CONSTANT DOMAIN IS UNDERLINED  SEQ ID NO: 131 EVQLVESGGGLVQPGGSLRLSCAASGFSLNNYWMSWVRQAPGKGLEWIGTISSGAYTWFATWATGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARYSSTTDWTYFNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDK THTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 330F11 HUMANIZED HEAVY CHAIN VARIABLE HEAVY CHAIN AMINO ACID SEQUENCE. COMPLIMENTARITY DETERMINING REGIONS ARE UNDERLINED  SEQ ID NO: 132 EVQLVESGGGLVQPGGSLRLSCAASGFSLNNYWMSWVRQAPGKGLEWIGTISSGAYTWFATWATGRFTISRDNSK NTLYLQMNSLRAEDTAVYYCARYSSTTDWTYFNIWGQGTLVTVSS 

What is claimed is:
 1. An isolated mAb having a binding specificity to human ROR1, comprising a light chain comprising SEQ ID NO:76 and a heavy chain comprising SEQ ID NO:80.
 2. The isolated mAb according to claim 1, having a binding affinity to human ROR1 with a Kd not greater than 70 nM.
 3. The isolated mAb according to claim 1, exhibiting one or more functional properties selected from high affinity binding to human ROR1, inhibiting human ROR1 activity, induction of apoptosis, regulation of EGFR signalling pathway, upregulation of EMT genes, enhancing T cell activation, stimulating antibody response, reversing the suppressive function of an immunosuppressive cell, or a combination thereof.
 4. The isolated mAb according to claim 1, wherein the isolated mAb comprises a humanized antibody, a chimeric antibody, a recombinant antibody, a bispecific antibody, tri-specific antibody, multi-specific antibody, an IgG, a Fv, a Fab, a F(ab′)2, a scFV or a scFV2 fragment.
 5. An isolated mAb having a binding specificity to human ROR1, wherein the isolated mAb comprises complementarity determining region (CDR)1, CDR2, and CDR3 of SEQ ID NO: 76 and CDR1, CDR2, and CDR3 of SEQ ID NO:80.
 6. An isolated nucleic acid encoding the isolated mAb Of according to claim 1 or
 5. 7. An expression vector comprising the isolated nucleic acid of claim 6, wherein the vector is expressible in a cell.
 8. A host cell comprising the nucleic acid of claim 6, wherein the host cell is a prokaryotic cell or a eukaryotic cell.
 9. A method of producing an antibody comprising culturing the host cell of one of claim 8, so that the antibody is produced.
 10. A pharmaceutical composition, comprising the isolated mAb Of thereof according to claim 1 or 5 or and a pharmaceutically acceptable carrier.
 11. The pharmaceutical composition of claim 10, further comprising a chemotherapeutic agent, a growth inhibitory agent, a drug unit from class of calicheamicin, an antimitotic agent, a toxin, a radioactive isotope, a therapeutic agent, an anti-estrogen agent, a receptor tyrosine kinase inhibitor, a kinase inhibitor, a cell cycle inhibitor, a DNA, RNA or protein synthesis inhibitor, a RAS inhibitor, or a combination thereof. 